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Smartox/Phrixotoxin-2，一种Kv4.2和Kv4.3通道阻滞剂/PHX002-00500/0.5mg
Phrixotoxin-2 (PaTx2)hasbeenisolatedoriginallyfromthevenomoftheChilefiretarantula Phrixotrichusauratus. Phrixotoxin-2 isa31aminoacidpeptidethatcontainsthreedisulfidebridges. Phrixotoxin-2 specificallyblocksrecombinant Kv4.2 and Kv4.3 currentswithIC50 valuesof34nMand71nM,respectively.Itdoessobyalteringthegatingpropertiesofthechannels.TheinhibitionofKv4.2andKv4.3currentsisfullyreversIBLeuponwashout.Kv4.1isonlyslightlysensitiveto Phrixotoxin-2 (maximalblockof20by300nM).Kv1,Kv2andKv3channelsubfamiliesareinsensitivetothistoxin.
Description:
AAsequence:Tyr-Cys2-Gln-Lys-Trp-Met-Trp-Thr-Cys9-Asp-Glu-Glu-Arg-Lys-Cys15-Cys16-Glu-Gly-Leu-Val-Cys21-Arg-Leu-Trp-Cys25-Lys-Arg-Ile-Ile-Asn-Met-NH2
Disulfidebonds:Cys2-Cys16,Cys9-Cys21 andCys15-Cys25
Length(aa):31
Formula:C169H259N49O43S8
MolecularWeight: 3921.71Da
Appearance:whitelyophilizedsolid
Solubility:waterorsalinebuffer
CASnumber:221889-63-0
Source:Synthetic
Purityrate:>95%
Reference:
EffectsofphrixotoxinsontheKv4familyofpotassiumchannelsandimplicationsfortheroleofIto1incardiacelectrogenesis
Inthepresentstudy,twonewpeptides,phrixotoxinsPaTx1&PaTx2(29-31aminoacids),whichpotentlyblockA-typepotassiumcurrents,havebeenpurifiedfromthevenomofthetarantulaPhrixotrichusauratus.2.PhrixotoxinsspecificallyblockKv4.3&Kv4.2currentsthatunderlieI(to1),withan5<IC50<70nM,byalteringthegatingpropertiesofthesechannels.3.NeitheraretheShaker(Kv1),Shab(Kv2)&Shaw(Kv3)subfamiliesofcurrents,norHERG,KvLQT1/IsK,inhibitedbyphrixotoxinswhichappearspecificoftheShal(Kv4)subfamilyofcurrents&alsoblockI(to1)inisolatedmurinecardiomyocytes.4.InordertoevaluatethephysiologicalconsequencesoftheIto1inhibition,micewereinjectedintravenouslywithPaTx1,whichresultedinnumeroustransientcardiacadversereactionsincludingtheoccurrenceofprematureventricularbeats,ventriculartachycardia&differentdegreesofatrioventricularblock.5.Theanalysisofthemouseelectrocardiogramshowedadose-dependentprolongationoftheQTinterval,chosenasasurrogateMarkerfortheirventricularrepolarization,from249+/-11to265+/-8ms(P<0.05).6.Itwasconcludedthatphrixotoxins,arenew&specificblockersofKv4.3&Kv4.2potassiumcurrents,&henceofI(to1)thatwillenablefurtherstudiesofKv4.2&Kv4.3channel&/orI(to1)expression.
DiochotS.E, etal. (1999)EffectsofphrixotoxinsontheKv4familyofpotassiumchannelsandimplicationsfortheroleof Ito1 incardiacelectrogenesis. BritishJournalofPharmacology. PMID: 10051143
TheEffectsofPutativeK+ChannelBlockersonVolumeRegulationofMurineSpermatozoa
Volumeregulationisanecessarytaskforspermatozoaastheosmolarityoffemaletractfluidsislowerthanthatintheepididymis&becausethedisruptionofitintransgenicmiceresultsininfertility.Asthespecificmechanismsbehindthisphenomenonareunknown,spermatozoafrommicewerescreenedforsensitivitiestoinhibitorsknowntoaffectspecificchannelsinvolvedinvolumeregulationofsomaticcells.Spermatozoafromthecaudaepididymidiswereexposedtophysiologicalhypotonicconditionswith&withoutinhibitor.Flowcytometricforwardscattermeasurementsweretakentoindicaterelativespermsizeat5&75minofincubation.Thepresenceofquinine(0.8mM),cadmium(0.2mM),flecainide(100microM),4-aminopyridine(4mM),barium(1mM),clofilium(10microM),&phrixotoxin(100nM)for75minresultedinsignificantlyhigherforwardscattervaluesthanspermincubatedinmediumwithoutaninhibitor.Theseresultsimplythatchannelspotentiallyinvolvedinvolumeregulationofmurinespermatozoaincludethevoltage-dependentKv1.4(alsoknownasKCNA1),Kv1.5(KCNA5),Kv4.1(KCND1),Kv4.2(KCND2),Kv4.3(KCND3),mink(KCNE1),&acid-sensitiveTASK2(KCNK5)&TASK3(KCNK9).WesternblotsconfirmedthepresenceofKv1.5&TASK2proteinsinspermplasmamembranesatsimilar(Kv1.5)orhigher(TASK2)molecularweightthaninsomaticcells.IncubationinadifferentpHdidnotrevealacidsensitivityofvolumeregulation.Volumeregulationofspermatozoamayinvolvenovelvoltage-gated&pH-sensitivepotassiumchannels,whichcouldbevaluabletargetsforthedevelopmentofaposttesticularmalecontraceptive.
BarfieldJ.P., etal. (2005)TheEffectsofPutativeK+ChannelBlockersonVolumeRegulationofMurineSpermatozoa.Biolreprod. PMID: 15673604
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